The proposed research deals with the processes of peptide hormone biosynthesis and secretion from three endocrine cell types: the insulin producing pancreatic beta-cell, the glucagon producing pancreatic alpha-cell and the enteroglucagon producing cells of the small intestine. An investigation of the mechanisms for and control of the processes of hormone biosynthesis and hormone secretion in these cell types hopefully will eventually clarify the means by which the body regulates the utilization of food stuffs and identify possible sites of malfunction in disease states such as diabetes mellitus. Through the measurement of insulin secretion from isolated pancreatic islets of the rat, the careful selection of agents causing and affecting insulin release and the use of radioactive metabolic probes, a variety of processes ultimately involved the use of radioactive metabolic probes, a variety of processes ultimately involved in the mechanism of insulin biosynthesis and secretion will be investigated. The processes include the recognition of insulin secretogogs by the beta-cell, the evolution and utilization of metabolic energy in the secretory process, and the modulation of the secretory response by intracellular metabolites. Parameters of endocrine cell function similar to those described above will also be studied in relation to glucagon biosynthesis and secretion using isolated islets once again, but under conditions selecting for high levels of alpha-cell function. Particular emphasis will be given the nature of glucagon biosynthesis via its precursor hormone and the isolation of the precursor form from bovine or porcine pancreata. The isolation of enteroglucagon from procine or bovine intestine and studies of its in vitro biosynthesis and secretion using incubated segments or sacs of small intestine of the rat also will be initiated with a view towards identifying the chemical structure and physiological significance of this hormone.